Homodimerization of IL-2 receptor beta chain is necessary and sufficient to activate Jak2 and downstream signaling pathways.
Cytokine receptor signaling involves the Jak/Stat pathways. Heterotrimeric IL-2R (alpha, beta, gamma[c] chains) activates Jak1 and Jak3, whereas homodimeric PRLR activates Jak2. The requirements directing such specificity of Jak activation are unknown. We show that chimeric receptors containing the intracellular domain of IL-2Rbeta chain fused to the extracellular domain of either EPOR or Kit, a non-cytokine receptor, activate Jak2. This observation provides evidence that IL-2Rbeta intrinsically possesses the ability to activate Jak2, but that this property is only displayed in homodimerized complexes. Our data suggest a role for the stoichiometry of cytokine receptors in selective activation of Janus kinases.
Ferrag
F
F
INSERM Unité 344 - Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris, France.
Pezet
A
A
Chiarenza
A
A
Buteau
H
H
Nelson
B H
BH
Goffin
V
V
Kelly
P A
PA
D000818:Animals; D016466:CHO Cells; D002364:Caseins / Q000096:biosynthesis / Q000235:genetics; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D053614:Janus Kinase 2; D051379:Mice; D008894:Milk Proteins; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D011981:Receptors, Prolactin / Q000096:biosynthesis / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection
D002364:Caseins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D015375:Receptors, Interleukin-2; D011981:Receptors, Prolactin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D004921:Erythropoietin; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2